Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Jennie G. Pouget, Vanessa F. Gonçalves, Erika L. Nurmi, Christopher P Laughlin, Karyn S. Mallya, James T. McCracken, Michael G. Aman, Christopher J. McDougle, Lawrence Scahill, Virginia L. Misener, Arun K. Tiwari, Clement C. Zai, Eva J. Brandl, Daniel Felsky, Amy Q. Leung, Jeffrey A. Lieberman, Herbert Y. Meltzer, Steven G. Potkin, Charlotte Niedling, Werner SteimerStefan Leucht, Jo Knight, Daniel J. Müller*, James L. Kennedy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Aim: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. Patients & methods: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). Results: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10-3), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10-3) and RUPP samples (p = 2.76 × 10-4). Conclusion: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 201.

Original languageEnglish (US)
Pages (from-to)5-22
Number of pages18
JournalPharmacogenomics
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • SLC25A4
  • TSPO
  • adenine nucleotide translocator
  • antipsychotic
  • genetics
  • mitochondria
  • peripheral benzodiazepine receptor
  • pharmacogenomics
  • schizophrenia
  • translocator protein-18 kDa
  • weight gain

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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